The decision to move the Africa Cup of Nations back to January could see more than 30 current Premier League players miss up to six matches and could "put managers off" making signings.
The 2019 tournament - won by Algeria - was held in June and July but next year's edition has been moved back to January.
Premier League leaders Liverpool could lose Senegal's Sadio Mane, Egypt's Mohamed Salah and Guinea's Naby Keita for a month next season.
"It definitely affects your thinking when it comes to signing African players," former Tottenham boss Harry Redknapp told BBC World Service.
"Invariably when they come back from the tournament, they're not the same. They don't seem to recover from the rigours of the Cup of Nations."
- 2021 Africa Cup of Nations moved back to January
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Why has the tournament moved?
The 2017 decision to move the start of the competition to June, from January, was widely welcomed, especially by top European clubs.
But next year's competition will take place from 9 January to 6 February, 2021, having been moved because of weather conditions in host country Cameroon - where there were highs of 33C on Wednesday.
The change also means that the tournament will not clash with the expanded Club World Cup, being held in China in June 2021.
"You'll suddenly lose players for six to eight weeks because they will go away to a training camp before," Redknapp told the Sport Today programme.
"When you're signing players, you do look at it and if they're going away to the Cup of Nations, sometimes you think: 'I'll give this one a miss.'
'I've lost contracts because of the tournament'
Further down the footballing pyramid, the move could also hamper a player's club career.
Dagenham & Redbridge defender Gabriel Zakuani - a former DR Congo captain and Peterborough, Northampton and Gillingham player - says he missed out on signing for clubs in the past because he would be away for so long during the season.
"I've had offers of a new contract taken off the table because I decided to go to the Cup of Nations," he told Sport Today.
"I can understand it from the point of view of managers but we want to go and we want to win it. I've had managers pulling their hair out every time I've had to go but it's tradition.
"The weather is better in that period in Cameroon [the winter]; we need the best Cup of Nations for African football and that's the right time to play it. It's as important in a career as anything else."
Who would my club miss?
Which players could your Premier League club be without next season? Based on internationals in current squads, and assuming all listed nations qualified:
Arsenal - Pierre-Emerick Aubmaeyang (Gabon), Nicolas Pepe (Ivory Coast), Mohamed Elneny (Egypt - currently on loan at Besiktas)
Aston Villa - Marvelous Nakamba (Zimbabwe), Trezeguet (Egypt), Jonathan Kodjia (Ivory Coast), Ahmed Elmohamady (Egypt)
Brighton - Leon Balogun (Nigeria), Yves Bissouma (Mali), Gaetan Bong (Cameroon), Percy Tau (South Africa - currently on loan at Club Brugge)
Crystal Palace - Jeffrey Schlupp (Ghana), Cheikhou Kouyate (Senegal), Jordan Ayew (Ghana), Wilfried Zaha (Ivory Coast)
Everton - Alex Iwobi (Nigeria), Jean-Philippe Gbamin (Ivory Coast), Oumar Niasse (Senegal), Yannick Bolasie (DR Congo - currently on loan at Sporting Lisbon)
Leicester City - Kelechi Ịheanachọ (Nigeria), Wilfred Ndidi (Nigeria), Daniel Amartey (Ghana), Islam Slimani (Algeria - currently on loan at Monaco), Rachid Ghezzal (Algeria - currently on loan at Fiorentina)
Liverpool - Naby Keita (Guinea), Mohamed Salah (Egypt), Sadio Mane (Senegal). Joel Matip (Cameroon) has retired from international football.
Manchester City - Riyad Mahrez (Algeria)
Manchester United - Eric Bailly (Ivory Coast)
Newcastle - Christian Atsu (Ghana), Henri Saivet (Senegal)
Southampton - Moussa Djenepo (Mali), Sofiane Boufal (Morocco), Mario Lemina (Gabon - currently on loan at Galatasaray)
Tottenham - Victor Wanyama (Kenya), Serge Aurier (Ivory Coast)
Watford - Isaac Success (Nigeria), Ismaila Sarr (Senegal)
West Ham - Arthur Masuaku (DR Congo)
Wolves - Romain Saiss (Morocco)